DK2451844T3 - Tlr3-bindingsmidler - Google Patents

Tlr3-bindingsmidler Download PDF

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Publication number
DK2451844T3
DK2451844T3 DK10734092.9T DK10734092T DK2451844T3 DK 2451844 T3 DK2451844 T3 DK 2451844T3 DK 10734092 T DK10734092 T DK 10734092T DK 2451844 T3 DK2451844 T3 DK 2451844T3
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antibody
tlr3
antibodies
amino acid
ser
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DK10734092.9T
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English (en)
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Laurent Gauthier
Catherine Massacrier
Yannis Morel
Carine Paturel
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Innate Pharma
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/54—F(ab')2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Diabetes (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Endocrinology (AREA)
  • Cell Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
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  • Gastroenterology & Hepatology (AREA)
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Claims (15)

1. Monoklonalt antistof, der specifikt binder et humant TLR3-polypeptid, hvor antistoffet hæmmer signalering ved hjælp af TLR3-polypeptidet uden at blokere binding af en dsRNA-TLR3-ligand til TLR3-polypeptidet, hvor antistoffet binder specifikt til TLR3-polypeptidet under neutrale betingelser ved et pH på mellem 6,6 og 7,4 og under sure betingelser ved et pH på mellem 4,5 og 6,5 med en subnanomolær KD for dets bivalente bindingsaffinitet; hvor antistoffet konkurrerer om binding til et TLR3-polypeptid med et antistof, der er udvalgt fra gruppen, der består af: (a) et antistof med et VH- og VL-område ifølge henholdsvis SEQ ID NO: 34 og 35 og (b) et antistof med et VH- og VL-område ifølge henholdsvis SEQ ID NO: 2 og 3.
2. Antistof ifølge krav 1, hvor antistoffet binder specifikt til TLR3-polypeptidet under sure betingelser med en 100 pikomolær eller bedre KD for dets bivalente bindingsaffinitet.
3. Antistof ifølge krav 1 til 2, hvor antistoffet er udvalgt fra gruppen, der består af: (a) et antistof med (i) tung kæde-CDR 1, 2 og 3 (HCDR1, HCDR2, HCDR3)-aminosyresekvenserne ifølge henholdsvis SEQ ID NO: 4, 5 og 6 og (ii) let kæde-CDR 1, 2 og 3 (LCDR1, LCDR2, LCDR3) -aminosyresekvenserne ifølge henholdsvis SEQ ID NO: 7, 8 og 9; og (b) et antistof med (i) tung kæde-CDR 1, 2 og 3 (HCDR1, HCDR2, HCDR3)-aminosyresekvenserne ifølge henholdsvis SEQ ID NO: 36, 37 og 38 og (ii) let kæde-CDR 1, 2 og 3 (LCDR1, LCDR2, LCDR3) -aminosyresekvenserne ifølge henholdsvis SEQ ID NO: 39, 40 og 41.
4. Antistof ifølge krav 1 til 3, hvor antistoffet er et kimært, humant eller humaniseret antistof.
5. Antistof ifølge krav 4, hvor isotypen af antistoffet er et IgG4.
6. Antistof ifølge krav 1 til 5, hvor antistoffet omfatter et Fc-områder, der er modificeret til reducering af dets FcyR-binding.
7. Antistof ifølge krav 1 til 6, hvor antistoffet er et antistoffragment, der er udvalgt blandt Fab, Fab', Fab'-SH, F(ab')2/ Fv, diabodies, enkeltkædet antistoffragment eller et multispecifikt antistof, der omfatter mangfoldige forskellige antistoffragmenter.
8. Antistof ifølge krav 1 til 7, hvor antistoffet er konjugeret eller kovalent bundet til en toksisk del.
9. Antistof ifølge krav 1 til 8, hvor antistoffet er i stand til at blive internaliseret af en TLR3-udtrykkende celle.
10. Antistof ifølge krav 1 til 9, hvor antistoffet er konjugeret eller kovalent bundet til en påviselig del.
11. Antistof ifølge krav 1 til 10, hvor antistoffet er dannet ved immunisering af et non-humant dyr med et immunogen, der omfatter et TLR3-polypeptid.
12. Hybridom eller rekombinant værtscelle, der danner antistoffet ifølge krav 1 til 11.
13. Farmaceutisk præparat, der omfatter et antistof ifølge et hvilket som helst af kravene 1-11 og et farmaceutisk acceptabelt bæremateriale.
14. Farmaceutisk præparat ifølge krav 13 til anvendelse til behandling eller forebyggelse af en sygdom, der er udvalgt fra gruppen, der består af autoimmunitet, inflammation, allergi, astma, infektion, cirrose og sepsis.
15. Farmaceutisk præparat ifølge krav 13 til anvendelse til behandling eller forebyggelse af en cancer.
DK10734092.9T 2009-07-10 2010-07-09 Tlr3-bindingsmidler DK2451844T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US22454809P 2009-07-10 2009-07-10
PCT/EP2010/059946 WO2011004028A2 (en) 2009-07-10 2010-07-09 Tlr3 binding agents

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DK2451844T3 true DK2451844T3 (da) 2015-07-27

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US (2) US9388246B2 (da)
EP (1) EP2451844B1 (da)
JP (1) JP5800809B2 (da)
CN (1) CN102471382A (da)
AU (1) AU2010270163B2 (da)
CA (1) CA2766747C (da)
DK (1) DK2451844T3 (da)
ES (1) ES2543095T3 (da)
RU (1) RU2562865C2 (da)
WO (1) WO2011004028A2 (da)

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CA2766747A1 (en) 2011-01-13
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US9388246B2 (en) 2016-07-12
CA2766747C (en) 2019-04-02
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EP2451844B1 (en) 2015-04-22
ES2543095T3 (es) 2015-08-14
WO2011004028A9 (en) 2011-08-11
WO2011004028A3 (en) 2011-05-19
AU2010270163A1 (en) 2012-02-02
JP2012532851A (ja) 2012-12-20
EP2451844A2 (en) 2012-05-16
US20120034232A1 (en) 2012-02-09
AU2010270163B2 (en) 2016-05-05
JP5800809B2 (ja) 2015-10-28
US20160347853A1 (en) 2016-12-01

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